NCT00035321

Brief Summary

The purposes of this study are to determine:

  • Whether olanzapine plus fluoxetine in combination will help patients with treatment-resistant major depression.
  • The safety of olanzapine plus fluoxetine in combination, plus and any side effects that might be associated with the combination.
  • The effectiveness of olanzapine plus fluoxetine compared to olanzapine and fluoxetine alone.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
600

participants targeted

Target at P75+ for phase_3 major-depressive-disorder

Timeline
Completed

Started Apr 2002

Longer than P75 for phase_3 major-depressive-disorder

Geographic Reach
2 countries

33 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2002

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

May 2, 2002

Completed
1 day until next milestone

First Posted

Study publicly available on registry

May 3, 2002

Completed
3.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2005

Completed
Last Updated

July 24, 2006

Status Verified

July 1, 2006

First QC Date

May 2, 2002

Last Update Submit

July 21, 2006

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (5)

  • To assess the efficacy of up to 8 weeks of treatment with OFC versus olanzapine and fluoxetine monotherapies, in patients with recurrent MDD without psychotic features

  • who meet study criteria for TRD, as measured by last observation carried forward (LOCF) mean change from baseline to endpoint in the MADRS total score

  • Treatment-resistant depression will be defined as:historic failure to achieve satisfactory response to an antidepressant (other than fluoxetine) during the current MDD episode

  • when treated with an acceptable antidepressant drug and dose for at least 6 weeks

  • prospective failure to achieve a satisfactory response to fluoxetine monotherapy during the 8 week study lead-in phase

Secondary Outcomes (16)

  • To compare the efficacy, safety, and quality of life results of up to 8 weeks of OFC therapy(treatment phase) with fluoxetine and olanzapine monotherapies using the following assessments:

  • Onset of action as measured by time to achieve and initial response (greater than or equal to 25% reduction from baseline in MADRS total score

  • Efficacy in the treatment of co-morbid anxiety symptoms as measured by LOCF mean change from baseline to endpoint in Hamilton Psychiatric Rating Scale for Anxiety (HAM-A)total score

  • Study-defined response and remission rates including time to achieve a full response (defined as greater than or equal to 50% reduction in MADRS total score)

  • and time to achieve remission (defined as MADRS total score less than or equal to 10 at endpoint)

  • +11 more secondary outcomes

Interventions

OlanzapineDRUG
FluoxetineDRUG

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male or female patients, 18 - 65 years of age.
  • Each patient must have a level of understanding sufficient to perform all tests and examinations required by the protocol, and must be considered reliable according to the investigator's clinical judgement
  • Patients must fulfill the criteria for recurrent MDD without psychotic features as defined by the DSM-IV, based on clinical assessment and confirmed by Structured Clinical Interview for DSM-IV Axis I Disorders - Clinical Version (SCID-I) plus the Major Depressive Disorder Specifiers included in the Research Version of the SCID-I. This includes at least one of the following diagnoses: 296.31, 296.32, and 296.33
  • Female patients of childbearing potential must be using a medically accepted means of contraception throughout the course of the study. Use of any oral or injectable contraception must be initiated prior to visit 2
  • Failure to achieve satisfactory antidepressant response to an adequate trial of an antidepressant (except fluoxetine), for at least 6 weeks at an acceptable dose or greater, occurring within the current episode of MDD

You may not qualify if:

  • Treatment with a drug within the last 30 days that has not received regulatory approval at the time of study entry
  • Exposure to OFC in a Lilly-sponsored clinical trial investigating OFC, and any patients historically failing to respond to olanzapine and fluoxetine in combination under any circumstance
  • Persons who have previously entered any Lilly-sponsored study which was investigating olanzapine
  • Female patients who are either pregnant or nursing
  • Serious, unstable illnesses for which death is anticipated within 1 year of intensive care unit hospitalization for the disease is anticipated within 6 months. This includes hepatic (specifically any degree of jaundice), renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic diseases (specifically current agranulocytosis with an absolute neutrophil count \< 500 mm\_3)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (33)

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Oceanside, California, United States

Location

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San Marcos, California, United States

Location

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Torrance, California, United States

Location

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New London, Connecticut, United States

Location

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Coral Springs, Florida, United States

Location

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North Miami, Florida, United States

Location

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St. Petersburg, Florida, United States

Location

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Atlanta, Georgia, United States

Location

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Marietta, Georgia, United States

Location

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Chicago, Illinois, United States

Location

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Libertyville, Illinois, United States

Location

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Oak Brook, Illinois, United States

Location

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New Orleans, Louisiana, United States

Location

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Baltimore, Maryland, United States

Location

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Glen Burnie, Maryland, United States

Location

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Westminster, Maryland, United States

Location

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Pittsfield, Massachusetts, United States

Location

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Columbia, Missouri, United States

Location

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Clementon, New Jersey, United States

Location

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Moorestown, New Jersey, United States

Location

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Toms River, New Jersey, United States

Location

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Dayton, Ohio, United States

Location

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Medford, Oregon, United States

Location

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Salem, Oregon, United States

Location

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Sellersville, Pennsylvania, United States

Location

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Lincoln, Rhode Island, United States

Location

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Dallas, Texas, United States

Location

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Salt Lake City, Utah, United States

Location

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Richmond, Virginia, United States

Location

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Waukesha, Wisconsin, United States

Location

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St. John's, Newfoundland and Labrador, Canada

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Kingston, Ontario, Canada

Location

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St. John's, Canada

Location

Related Publications (5)

  • Houston JP, Kohler J, Bishop JR, Ellingrod VL, Ostbye KM, Zhao F, Conley RR, Poole Hoffmann V, Fijal BA. Pharmacogenomic associations with weight gain in olanzapine treatment of patients without schizophrenia. J Clin Psychiatry. 2012 Aug;73(8):1077-86. doi: 10.4088/JCP.11m06916.

    PMID: 22967772DERIVED

  • Houston JP, Lau K, Aris V, Liu W, Fijal BA, Heinloth AN, Perlis RH. Association of common variations in the norepinephrine transporter gene with response to olanzapine-fluoxetine combination versus continued-fluoxetine treatment in patients with treatment-resistant depression: a candidate gene analysis. J Clin Psychiatry. 2012 Jun;73(6):878-85. doi: 10.4088/JCP.10m06744. Epub 2012 Mar 6.

    PMID: 22480387DERIVED

  • Houston J, Dharia S, Bishop JR, Ellingrod VL, Fijal B, Jacobson JG, Hoffmann VP. Association of DRD2 and ANKK1 polymorphisms with prolactin increase in olanzapine-treated women. Psychiatry Res. 2011 May 15;187(1-2):74-9. doi: 10.1016/j.psychres.2010.10.020. Epub 2010 Nov 20.

    PMID: 21095016DERIVED

  • Tohen M, Case M, Trivedi MH, Thase ME, Burke SJ, Durell TM. Olanzapine/fluoxetine combination in patients with treatment-resistant depression: rapid onset of therapeutic response and its predictive value for subsequent overall response in a pooled analysis of 5 studies. J Clin Psychiatry. 2010 Apr;71(4):451-62. doi: 10.4088/JCP.08m04984gre. Epub 2010 Feb 23.

    PMID: 20361905DERIVED

  • Thase ME, Corya SA, Osuntokun O, Case M, Henley DB, Sanger TM, Watson SB, Dube S. A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, and fluoxetine in treatment-resistant major depressive disorder. J Clin Psychiatry. 2007 Feb;68(2):224-36. doi: 10.4088/jcp.v68n0207.

    PMID: 17335320DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

OlanzapineFluoxetine

Condition Hierarchy (Ancestors)

Depressive DisorderMood DisordersMental Disorders

Intervention Hierarchy (Ancestors)

BenzodiazepinesBenzazepinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsPropylaminesAminesOrganic Chemicals

Study Officials

  • Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

    Eli Lilly and Company

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY

Study Record Dates

First Submitted

May 2, 2002

First Posted

May 3, 2002

Study Start

April 1, 2002

Study Completion

July 1, 2005

Last Updated

July 24, 2006

Record last verified: 2006-07

Locations

CA(3)US(30)